BACKGROUND: Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs). AIMS: To test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants. METHOD: In an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163). RESULTS: Altogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score at 6 weeks was 0.50 (95% CI -2.04 to 3.03, P = 0.70), which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype. CONCLUSIONS: It is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression.
BACKGROUND: Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs). AIMS: To test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants. METHOD: In an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163). RESULTS: Altogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score at 6 weeks was 0.50 (95% CI -2.04 to 3.03, P = 0.70), which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype. CONCLUSIONS: It is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression.
Authors: Maciej Trzaskowski; Divya Mehta; Wouter J Peyrot; David Hawkes; Daniel Davies; David M Howard; Kathryn E Kemper; Julia Sidorenko; Robert Maier; Stephan Ripke; Manuel Mattheisen; Bernhard T Baune; Hans J Grabe; Andrew C Heath; Lisa Jones; Ian Jones; Pamela A F Madden; Andrew M McIntosh; Gerome Breen; Cathryn M Lewis; Anders D Børglum; Patrick F Sullivan; Nicholas G Martin; Kenneth S Kendler; Douglas F Levinson; Naomi R Wray Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2019-02-01 Impact factor: 3.568
Authors: Stephan Ripke; Naomi R Wray; Cathryn M Lewis; Steven P Hamilton; Myrna M Weissman; Gerome Breen; Enda M Byrne; Douglas H R Blackwood; Dorret I Boomsma; Sven Cichon; Andrew C Heath; Florian Holsboer; Susanne Lucae; Pamela A F Madden; Nicholas G Martin; Peter McGuffin; Pierandrea Muglia; Markus M Noethen; Brenda P Penninx; Michele L Pergadia; James B Potash; Marcella Rietschel; Danyu Lin; Bertram Müller-Myhsok; Jianxin Shi; Stacy Steinberg; Hans J Grabe; Paul Lichtenstein; Patrik Magnusson; Roy H Perlis; Martin Preisig; Jordan W Smoller; Kari Stefansson; Rudolf Uher; Zoltan Kutalik; Katherine E Tansey; Alexander Teumer; Alexander Viktorin; Michael R Barnes; Thomas Bettecken; Elisabeth B Binder; René Breuer; Victor M Castro; Susanne E Churchill; William H Coryell; Nick Craddock; Ian W Craig; Darina Czamara; Eco J De Geus; Franziska Degenhardt; Anne E Farmer; Maurizio Fava; Josef Frank; Vivian S Gainer; Patience J Gallagher; Scott D Gordon; Sergey Goryachev; Magdalena Gross; Michel Guipponi; Anjali K Henders; Stefan Herms; Ian B Hickie; Susanne Hoefels; Witte Hoogendijk; Jouke Jan Hottenga; Dan V Iosifescu; Marcus Ising; Ian Jones; Lisa Jones; Tzeng Jung-Ying; James A Knowles; Isaac S Kohane; Martin A Kohli; Ania Korszun; Mikael Landen; William B Lawson; Glyn Lewis; Donald Macintyre; Wolfgang Maier; Manuel Mattheisen; Patrick J McGrath; Andrew McIntosh; Alan McLean; Christel M Middeldorp; Lefkos Middleton; Grant M Montgomery; Shawn N Murphy; Matthias Nauck; Willem A Nolen; Dale R Nyholt; Michael O'Donovan; Högni Oskarsson; Nancy Pedersen; William A Scheftner; Andrea Schulz; Thomas G Schulze; Stanley I Shyn; Engilbert Sigurdsson; Susan L Slager; Johannes H Smit; Hreinn Stefansson; Michael Steffens; Thorgeir Thorgeirsson; Federica Tozzi; Jens Treutlein; Manfred Uhr; Edwin J C G van den Oord; Gerard Van Grootheest; Henry Völzke; Jeffrey B Weilburg; Gonneke Willemsen; Frans G Zitman; Benjamin Neale; Mark Daly; Douglas F Levinson; Patrick F Sullivan Journal: Mol Psychiatry Date: 2012-04-03 Impact factor: 15.992
Authors: C O'Driscoll; J E J Buckman; E I Fried; R Saunders; Z D Cohen; G Ambler; R J DeRubeis; S Gilbody; S D Hollon; T Kendrick; D Kessler; G Lewis; E Watkins; N Wiles; S Pilling Journal: BMC Med Date: 2021-05-06 Impact factor: 8.775
Authors: Melanie Chalder; Nicola J Wiles; John Campbell; Sandra P Hollinghurst; Anne M Haase; Adrian H Taylor; Kenneth R Fox; Ceire Costelloe; Aidan Searle; Helen Baxter; Rachel Winder; Christine Wright; Katrina M Turner; Michael Calnan; Deborah A Lawlor; Tim J Peters; Deborah J Sharp; Alan A Montgomery; Glyn Lewis Journal: BMJ Date: 2012-06-06